2-amino-5-hydroxynaphthalene-1,7-disulphonic acid

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Eye irritation:

The ocular irritation potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Smiles notation: c1cc(c(c2c1c(cc(c2)S(=O)(=O)O)O)S(=O)(=O)O)N
- InChl: 1S/C10H9NO7S2/c11-8-2-1-6-7(10(8)20(16,17)18)3-5(4-9(6)12)19(13,14)15/h1-4,12H,11H2,(H,13,14,15)(H,16,17,18)
- Physical state: Solid
- Substance type: Organic

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not fully reversible within:

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and "k" )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aromatic amines AND Phenols AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Activated N-heterocycles OR Esters of organic sulfonic or sulfuric esters OR Inclusion rules not met OR Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=100%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR Not categorized OR Pirprofen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.99

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.507

Interpretation of results:

other: not irritating

Conclusions:

The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Smiles notation: c1cc(c(c2c1c(cc(c2)S(=O)(=O)O)O)S(=O)(=O)O)N
- InChl: 1S/C10H9NO7S2/c11-8-2-1-6-7(10(8)20(16,17)18)3-5(4-9(6)12)19(13,14)15/h1-4,12H,11H2,(H,13,14,15)(H,16,17,18)
- Physical state: Solid
- Substance type: Organic

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed.

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Anthrones OR Nitro-aromatic OR Polycyclic Aromatic Hydrocarbons OR Primary aromatic amine,hydroxyl amine and its derived esters OR Quinones by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.99

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.414

Interpretation of results:

other: not irritating

Conclusions:

The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studies has been investigated for the test chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)and its structurally similar read across substances 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, skin irritation potential was estimated for 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2). The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) is considered to be not irritating to the skin of rabbits.

 

The above results were supported by the skin irritation studies reported by GREIM H., et.al. (Chemosphere Vol. 28, No. 12, pp. 2203.2236, 1994) and BG Chemie (TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000) for two structurally similar read across substances 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7) on 2 New Zealand White rabbits (male and female). In both the studies, the approx. 500 mg of test chemical was applied to the inner surface of the ears of 2 rabbits under an adhesive dressing for 24 hours and observations were made upto 7 days. At the end of the exposure period, the test substance was washed off with water and soap/vegetable oil. No skin irritation was observed after 7 days. Hence the chemicals, 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7) was considered to be non-irritant to rabbit skin.

 

Based on the available data for the target chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)and its structurally similar read across substances 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7),it can be concluded that chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies, the test chemical 2 -amino-5 -hydroxynaphthalene-1,7 -disulfonic acid (CAS No: 6535 -70 -2) has been investigated to observe the potential for ocular irritation to a greater or lesser extent.The studies are based on in vivo experiments in rabbits for target chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)and its structurally similar read across substances 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, ocular irritation potential was estimated for 2 -amino-5 -hydroxynaphthalene-1,7 -disulfonic acid (CAS No: 6535 -70 -2) . The substance 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)is considered to be not irritating to the eyes of rabbits.

 

 The GREIM H., et.al. (Chemosphere Vol. 28, No. 12, pp. 2203.2236, 1994) and BG Chemie (TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000) conducted an eye irritation study for structurally similar read across substance7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) in rabbits. In this study, 50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals and each were observed for 7 days. No eye irritation was observed after 7 days. Hence the chemical 7-amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) can be considered non-irritant to rabbit eyes.

 

 

The above result was further supported by another eye irritation study conducted by GREIM H., et.al. (Chemosphere Vol. 28, No. 12, pp. 2203.2236, 1994) and BG Chemie (TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000) for structurally similar read across substance6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acidin rabbit. In this test, 50 mg of test chemical was instilled into the conjunctival sac of 2 rabbits. One hour after application, slight reddening was observed, which cleared up completely after 3 days. Hence, the substance 6-Amino-4-hydroxy-2 -naphthalene-6-sulfonic acid was considered to be not irritating to rabbit eyes.

 

Based on the available data for the target chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)and its structurally similar read across substances 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) and 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7),it can be concluded that chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)is not able to cause eye rritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)is unlikely to cause skin and eye irritation. Hence2-amino-5-hydroxynaphthalene-1,7-disulfonic acid (CAS No: 6535-70-2)can be classified under the category “Not Classified” for skin and eye as per CLP.